76 articles - From Friday Nov 25 2022 to Friday Dec 02 2022
Guidelines and related publications, position statements, white papers, technical reviews, consensus statements, etc…
| Blood Adv |
Comparison and validation of the 2022 European LeukemiaNet guidelines in acute myeloid leukemia. The updated ELN 2022 guidelines better stratify survival, namely between patients with intermediate or adverse-risk AML treated with IC. The increased complexity of risk stratification with inclusion of additional cytogenetic and molecular aberrations necessitates clinical workflows simplifying risk stratification. |
| Leukemia |
Diagnostics in Waldenström's macroglobulinemia: a consensus statement of the European Consortium for Waldenström's Macroglobulinemia. In this paper, we present the consensus recommendations and laboratory requirements for the diagnosis of WM developed by the European Consortium of Waldenström's Macroglobulinemia (ECWM), for both clinical practice as well as the research/academical setting. We provide the procedures for multiparametric flow cytometry, fluorescence in situ hybridization and molecular tests, and with this offer guidance for a standardized diagnostic work-up and methodological workflow of patients with IgM monoclonal gammopathy of uncertain significance, asymptomatic and symptomatic WM. |
meta-analyses and systematic reviews
| Haematologica |
| Leukemia |
| Thromb Haemost |
Diagnostic accuracy of V/Q and Q SPECT/CT in patients with suspected pulmonary embolism: a systematic review and meta-analysis. V/Q SPECT/CT has high sensitivity and specificity for the diagnosis of acute PE, meanwhile Q SPECT/CT has high sensitivity but limited specificity for the diagnosis of PE. Management studies will conclusively ascertain the actual role of SPECT/CT in the diagnostic workup of patients with suspected acute PE. |
RCT, clinical trials, retrospective studies, etc…
| Ann Oncol |
Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate and high-risk early stage triple negative breast cancer. c-TRAK-TN is the first prospective study to assess whether ctDNA assays have clinical utility in guiding therapy in TNBC. Patients had a high rate of metastatic disease on ctDNA detection. Findings have implications for future trial design, emphasising the importance of commencing ctDNA testing early, with more sensitive and/or frequent ctDNA testing regimes. |
| Blood |
Activation of the PP2A-B56a heterocomplex synergizes with venetoclax therapies in AML through BCL2 and MCL1 modulation. Finally, PP2A targeting increases the efficacy of the clinically approved venetoclax and azacitidine combination in vitro, in primary cells, and in an AML patient-derived xenograft model. These preclinical results provide a scientific rationale for testing PP2A-activating drugs with venetoclax combinations in AML. |
Associations of clonal haematopoiesis with recurrent vascular events and death in patients with incident ischemic stroke. D358A). The CH mutation profile is accompanied by a pro-inflammatory profile opening new avenues for preventive precision medicine approaches to resolve the self-perpetuating cycle of inflammation and clonal expansion. |
DDX41-associated susceptibility to myeloid neoplasms. Several aspects of deleterious germline DDX41 alleles are noteworthy: (i) Certain variants are common in particular populations; (ii) MNs develop at older ages typical of de novo disease, challenging the paradigm that inherited cancer risk always causes disease in young people; (iii) Despite equal frequencies of these variants in men and women, men progress to MNs more frequently, suggesting a gender-specific effect on myeloid leukemogenesis; and (iv) Individuals with deleterious germline DDX41 variants develop acute severe graft versus host disease after allogeneic hematopoietic cell transplantation with wild-type donors more than others unless they receive post-transplant cyclophosphamide, suggesting a pro-inflammatory milieu that stimulates donor-derived T-cells. Biochemical studies and animal models have identified DDX41's ability to interact with double stranded DNA and RNA:DNA hybrids with roles in mRNA splicing, rRNAs/snoRNAs processing, and modulation of innate immunity, disruption of which could promote inflammation and drive tumorigenesis. |
The Spectrum of GATA2 Deficiency Syndrome. Allogeneic hematopoietic stem cell transplantation (HSCT) results in reversal of the phenotype. There remain important unanswered questions in GATA2 deficiency including: 1) why do some family members remain asymptomatic despite harboring deleterious mutations in GATA2, 2) what are the genetic changes that lead to myeloid progression, 3) what causes the apparent genetic anticipation, and 4) what is the role of preemptive HSCT. |
| Blood Adv |
Activation priming and cytokine polyfunctionality modulate the enhanced functionality of low-affinity CD19 CAR T cells. Our results show that CAT CAR T-cells exhibit enhanced activation to CD19 stimulation and a distinct transcriptomic and protein profile, with increased activation and cytokine polyfunctionality compared to FMC63 CAR T-cells. We demonstrate that the enhanced functionality of low-affinity CAT CAR T-cells is a consequence of an antigen-dependent priming induced by residual CD19-expressing B-cells present in the manufacture. |
Cord blood transplantation for nonmalignant disorders: early functional immunity and high survival. We conclude that in the absence of a MRD, UCBT following myeloablative conditioning without serotherapy is an excellent curative option in young children with non-malignant disorders. This trial is registered at as NCT00950846. |
Incidence, Risk Factors, and Impact of Early Cardiac Toxicity after Allogeneic Hematopoietic Cell Transplantation. ECE was associated with higher NRM (HR 4.68, P<0.001) and lower OS (HR 3.03, P<0.001). Considering that PTCY and TBI were predictors for ECE, and the impact of this complication on transplant mortality, the implementation of cardiac monitoring plans could be appropriate in patients receiving these medications. |
Paired bone marrow and peripheral blood samples demonstrate lack of widespread dissemination of some CH clones. Importantly, we illustrate that CH, including clones with variant allele frequencies >10%, can be confined to specific bone marrow spaces and may be eliminated through surgical excision. Future work will define whether clones with somatic mutations in particular genes or clonal fractions of certain sizes are more likely to be localized or are slower to disseminate into the peripheral blood and other bony sites. |
Retained functional normal and preleukemic HSCs at diagnosis are associated to good prognosis in DNMT3Amut NPM1mut AMLs. Furthermore, we show that while CD34+ subpopulations can contain next to LSCs also normal and/or pre-leukemic Hematopoietic Stem Cells (HSCs), this is not the case in CD34-GPR56+NKG2DL- enriched LSCs which thus can be isolated with high purity. Finally, we show that AML patients, who retain at time of diagnosis a reserve of normal and/or preleukemic HSCs in their bone marrow able to reconstitute immunocompromised mice, have significant longer relapse-free and overall survival compared to AML patients in whom functional HSCs are no longer detectable. |
| Haematologica |
DUSP22 rearrangement is associated with distinctive immunophenotype but not outcome in patients with systemic ALK-negative anaplastic large cell lymphoma. However, in this cohort DUSP22-R was not associated with a better clinical outcome. Therefore, we suggest that current treatment guidelines for this subset of ALK-negative ALCL patients should not be modified at this time. |
ALK-negative anaplastic large cell lymphoma with DUSP22 rearrangement has distinctive disease characteristics with better progression-free survival: a LYSA study. There were 47/104 (45%) DUSP22-R and 2/93 (2%) TP63-R cases, including one DUSP22-R/TP63-R. DUSP22-R tumors showed more frequent CD3 expression (62% versus 35%, P=0.01), and less commonly a cytotoxic phenotype (27% versus 82%; P. |
Hyperactive CREB subpopulations increase during therapy in paediatric B lineage acute lymphoblastic leukaemia. The small molecule CREB inhibitor, 666-15, was shown to reduce CREB transcriptional activity and induce apoptosis in ALL PDX cells of varying cytogenetic subtypes in vitro, both in the presence and absence of stromal support. Together, these data suggest that the cAMP signalling pathway may provide an opportunity for MRD-directed therapy for many patients at high risk of relapse. |
Immune thrombotic thrombocytopenic purpura plasmas induce calcium- and IgG-dependent endothelial activation: correlations with disease severity. Furthermore, two anti-ADAMTS13 monoclonal antibodies purified from iTTP patient B cells, but not serum from hereditary TTP, induced endothelial Ca2+ flux associated with Weibel-Palade bodies exocytosis in vitro, whereas inhibition of endothelial ADAMTS13 expression using small interference RNA, significantly decreased the stimulating effects of iTTP IgG. In conclusion, Ca2+-mediated endothelial cell activation constitutes a second "hit" of iTTP, is correlated with the severity of the disease and may constitute a possible therapeutic target. |
Measurable residual disease in acute lymphoblastic leukemia: methods and clinical context in adult patients. However, new approaches to target MRD in patients with T-ALL remain an unmet need. As our MRD detection assays become more sensitive and expanding novel therapeutics enter clinical development, the future of ALL therapy will increasingly utilize MRD as a criterion to either intensify or modify therapy to prevent relapse or de-escalate therapy to reduce treatment-related morbidity and mortality. |
Measurable residual disease in chronic myeloid leukemia. In this review we track this development including the international collaboration to standardize results, discuss the integration of molecular monitoring with other factors that affect patients' management, and describe emerging technology. Four case histories describe varying scenarios in which the accurate measurement of residual disease identified patients at risk of disease progression and allowed appropriate investigations and timely clinical intervention. |
Targeting glutaminase is therapeutically effective in ibrutinib-resistant mantle cell lymphoma. Moreover, telaglenastat showed anti-MCL synergy when combined with ibrutinib or venetoclax in vitro, which was confirmed using an MCL patient-derived xenograft model. Our study provides the first evidence that targeting GLS with telaglenastat, alone or in combination with ibrutinib or venetoclax, is a promising strategy to overcome ibrutinib resistance in MCL. |
The present and future of measurable residual disease testing in acute myeloid leukemia. The principles and practices surrounding MRD remain incompletely determined however and the genetic and immunophenotypic heterogeneity of AML may prevent a one-sizefits- al approach. Here, we review the current approaches to MRD testing in AML, discuss strengths and limitations, highlight recent technological advances that may improve such testing, and summarize ongoing initiatives to generate the clinical evidence needed to advance the use of MRD testing in patients with AML. |
| J Hematol Oncol |
| Lancet Haematol |
A sex-informed approach to improve the personalised decision making process in myelodysplastic syndromes: a multicentre, observational cohort study. Interpretation Our results suggest that a sex-informed approach can improve the personalised decision making process in patients with myelodysplastic syndromes and should be considered in the design of clinical trials including low-risk patients. Funding European Union (Horizon 2020 and Transcan programs), Italian Association for Cancer Research, Italian Ministry of Health, and Italian Ministry of University and Research. |
| Leukemia |
Sustained activation of non-canonical NF- Collectively, our study uncovered novel molecular drivers of doxorubicin-induced resistance that are regulated by non-canonical NF- |
The ENL YEATS epigenetic reader domain critically links MLL-ENL to leukemic stem cell frequency in t(11;19) Leukemia. Therapeutically, YEATS containing MLL-ENL leukemic cells display increased sensitivity to the YEATS inhibitor SGC-iMLLT compared to control AML cells. Our results demonstrate that the YEATS domain is important for MLL-ENL fusion protein-mediated leukemogenesis and exposes an "Achilles heel" that may be therapeutically targeted for treating t(11; 19) patients. |
| Thromb Haemost |
Characterization of shear stress-mediated platelet dysfunction: An ex vivo model for extracorporeal circulation and a prospective clinical study. However, no correlation between platelet degranulation and the occurrence of bleeding or thromboembolic events was observed. The used whole Blood flow cytometry with immediately fixation after drawing introduces a sensitive and easy-to-use method to determine platelet activation status and our data confirm that increased shear stress conditions under ECC can cause impaired degranulation of platelet. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Ann Oncol |
Moving towards individualized target-based therapies in acute myeloid leukemia. We then propose approaches to optimize AML therapy in patients without directly actionable mutations. We conclude with a discussion on the emerging role of using measurable residual disease (MRD) to modify therapy based on the quality of response. |
| Blood |
| Blood Cancer J |
Chronic lymphocytic leukemia treatment algorithm 2022. The CLL-International Prognostic Index (CLL-IPI) remains the best-validated tool in predicting the time to first therapy among previously untreated patients, which guides selection for early intervention efforts. This review summarizes our current approach to the management of CLL, right from the time of diagnosis through relapsed disease. |
| Haematologica |
| Leukemia |
Biological drivers of clinical phenotype in myelofibrosis. Recent data indicate that an innate immune deregulated state that hinges on the myddosome-IRAK-NF |
misc publications eg case reports, tools of the trade, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Haematologica |
| Lancet Haematol |
| Leukemia |
Letters to the editors and authors’ replies
| Am J Hematol |
| Blood Cancer J |
| J Hematol Oncol |
Pre-exposure prophylaxis with tixagevimab/cilgavimab (AZD7442) prevents severe SARS-CoV-2 infection in recipients of allogeneic hematopoietic stem cell transplantation during the Omicron wave: a multicentric retrospective study of SFGM-TC. Only one major adverse event was reported: an acute coronary syndrome, resolved without sequelae. Pending randomized controlled trial results, our data support the use of AZD7442 as pre-exposure prophylaxis for COVID-19 during Omicron wave in allo-HSCT patients who failed to develop humoral immunity to vaccination, to prevent severe and potentially lethal forms of SARS-CoV-2 infection. |
| Leukemia |
Optical Genome Mapping in MDS and AML as tool for structural variant profiling-comment and data update on Yang et al.: "High-resolution structural variant profiling of myelodysplastic syndromes by optical genome mapping uncovers cryptic aberrations of prognostic and therapeutic significance". |